Evaluation of Adverse Events Experiencedby Older Patients Participatingin Studies of MolecularlyTargeted Agents Alone orin Combination CarolA.Townsley,GregoryR.Pond,AmitM.Oza,HalW.Hirte,EricWinquist,GlenwoodGoss, PamelaDegendorfer,MalcolmJ.Moore,andLillianL.Siu Abstract Background: The tolerability of molecularly targeted agents in older patients has not been specifically examined. Adverse event data from clinical trials in the Princess Margaret Hospital PhaseIIConsortiumdatabasewereanalyzedtoaddressthisquestion. Methods: The Consortium database collects trial information on all patients treated with either a molecularly targeted agent alone or in combination since 2001. The frequency of adverse events was determined and analyzed by two different age groups, <65 years and z65 years. Toxicity indices (TI) and frequencies of dose-limiting toxicities (DLT), based on adverse events of all causalities (TI ALL and DLT ALL ), and on adverse events that were at least possibly related to the molecularly targeted agent (TI MTA and DLT MTA ), were calculated for both age groups. Results: Four hundred and one patients who received 1,252 treatment cycles were analyzed from 19 different studies. Baseline performance status was similar between both age groups, but fewer older patients have had multiple prior regimens of chemotherapy or prior radiation therapy. A comparison of the proportions of younger and older patients experiencing DLT ALL and DLT MTA showed similar results. TheTI MTA values were comparable between the two age groups in both single agent (3.25 versus 3.00, for <65 versus z65 years) and multi-agent (3.65 versus 3.00, for <65 versus z65 years) trials. Conclusions: Older patients seem to tolerate molecularly targeted therapies either alone or in combination with chemotherapy as well as younger patients. Age alone should not be a barrier intheadministrationoftargetedagents. Individuals ages 65 years or over constitute the fastest growing segment of the North American population (1). In 2001, >50% of new cases of cancer and 67% of all cancer deaths occurred in people over the age of 65 years, thus making the effective care of the older patient with cancer an imperative goal (2). This geriatric population presents a significant challenge to the medical system, not only because of increasing numbers but also because of the complex health issues that often develop with increasing age (3). Attitudes toward the older patient affect their cancer management. Many health professionals associate chrono- logical age with poor prognosis, cognitive impairment, decreased quality of life, limited life expectancy, and decreased social worth (4). Thus, the older patient receives less screening for cancer, fewer staging tests, less aggressive therapy, and more often, no treatment at all (5). Older patients themselves may attribute cancer symptoms to the aging process, resulting in delayed diagnosis. Preconceived impressions of the toxicities from cancer therapies may also make older patients less likely to accept or request more aggressive treatments (6). Unfortunately, the current literature is not helpful in educating physicians who accept a stereotype that all older patients have poor tolerance to chemotherapy or radiation therapy. Many studies have investigated this phenomenon, but reports are contradictory. Several trials using cytotoxic therapy have shown an increased risk of toxicity including myelotox- icity in the elderly (7 – 13), although other studies have shown almost equivalent toxicity profiles between older and younger patients (14 – 18). Molecularly targeted agents are currently emerging as a new cancer treatment strategy. Theoretically, they are more specific against cancer targets than conventional cytotoxic chemother- apy, and as such, may be better tolerated by all patients, including those of more advanced age. As yet, no age-specific analysis evaluating the tolerability of molecularly targeted agents in this population have been reported. Cancer Therapy: Clinical Authors’Affiliation: Princess Margaret HospitalPhase IIConsortium, Ontario, Canada Received8/16/05;revised12/15/05;accepted12/21/05. Grant support: ClinicalTrialContractsfromtheU.S.NationalCancerInstitute,No. N01-CM-17107. Thecostsofpublicationofthisarticleweredefrayedinpartbythepaymentofpage charges.Thisarticlemustthereforebeherebymarked advertisement inaccordance with18U.S.C.Section1734solelytoindicatethisfact. Requestsforreprints: LillianL.Siu,PrincessMargaretHospital,UniversityHealth Network,610UniversityAvenue,Suite5-210,Toronto,Ontario,M5G2M9,Canada. Phone:416-946-2911;Fax:416-946-6546;E-mail:lillian.siu@uhn.on.ca. F 2006AmericanAssociationforCancerResearch. doi:10.1158/1078-0432.CCR-05-1798 www.aacrjournals.org ClinCancerRes2006;12(7)April1,2006 2141 Downloaded from http://aacrjournals.org/clincancerres/article-pdf/12/7/2141/1968400/2141.pdf by guest on 17 June 2022